Aims: The roles of tumour suppressor genes: adenomatous polyposis coli (APC) and E-cadherin (CDH1) were investigated in clear cell renal cell carcinoma.
Methods: Forty-five human clear cell renal cell carcinomas were tested for APC gene instability by polymerase chain reaction/loss of heterozygosity using the restriction fragment length polymorphism method. E-cadherin gene was analysed by PCR amplification of tetranucleotide marker (D16S752) and the alleles were visualised by PAGE/silver staining.
Results: The overall proportion of loss of heterozygosity of the APC gene was 37.5% (9/24). D16S752 marker linked to E-cadherin gene (informativeness 91%) revealed three samples with loss of heterozygosity (7.5%). Interestingly, replication error phenotype was detected in 9.1% of clear cell renal cell carcinoma samples. Multivariate statistical analysis of samples informative for both APC and E-cadherin genes showed that, in this data set, loss of heterozygosity of the APC gene is correlated with advanced age and more severe TNM stages. Genetic changes of the E-cadherin gene, on the other hand, appear to be correlated with younger age groups and less severe TNM stages.
Conclusions: Our results suggest that alterations, both in APC and E-cadherin genes, are involved in the evolution and progression of clear cell renal cell carcinoma. Microsatellite genetic instability of the E-cadherin gene indicates that another cellular mechanism, mismatch repair, may also be targeted in this malignancy.